Voltage-gated L-type Ca2+-channels have an important physiological role in pancreatic β-cell (“β-cell”) signal-transduction (1). These channels constitute an essential link between transient changes in membrane potential and insulin release from β-cells. Changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) in the β-cell are associated with the activation of a spectrum of intracellular signals and are strictly regulated, as prolonged high [Ca2+]i is harmful to the cells.
In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic β-cell. Sera from newly diagnosed type 1 diabetic (T1D) patients have been shown to increase the activity of voltage-gated L-type Ca2+-channels in β-cells resulting in increased [Ca2+]i upon depolarization and β-cell apoptosis, effects that can be prevented by Ca2+-channel blockers (2). However, it has not been determined what factor in T1D serum is responsible for the changes in [Ca2+]i.
We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free Ca2+ concentration ([Ca2+]i) and β-cell death.